PMID- 29038584
OWN - NLM
STAT- MEDLINE
DCOM- 20190628
LR  - 20190628
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Oct 16
TI  - Dual-Drug Containing Core-Shell Nanoparticles for Lung Cancer Therapy.
PG  - 13249
LID - 10.1038/s41598-017-13320-4 [doi]
LID - 13249
AB  - Late-stage diagnosis of lung cancer occurs ~95% of the time due to late 
      manifestation of its symptoms, necessitating rigorous treatment following 
      diagnosis. Existing treatment methods are limited by lack of specificity, 
      systemic toxicity, temporary remission, and radio-resistance in lung cancer 
      cells. In this research, we have developed a folate receptor-targeting 
      multifunctional dual drug-loaded nanoparticle (MDNP) containing a 
      poly(N-isopropylacrylamide)-carboxymethyl chitosan shell and poly 
      lactic-co-glycolic acid (PLGA) core for enhancing localized chemo-radiotherapy to 
      effectively treat lung cancers. The formulation provided controlled releases of 
      the encapsulated therapeutic compounds, NU7441 - a potent radiosensitizer, and 
      gemcitabine - an FDA approved chemotherapeutic drug for lung cancer 
      chemo-radiotherapy. The MDNPs showed biphasic NU7441 release and pH-dependent 
      release of gemcitabine. These nanoparticles also demonstrated good stability, 
      excellent hemocompatibility, outstanding in vitro cytocompatibility with alveolar 
      Type I cells, and dose-dependent caveolae-mediated in vitro uptake by lung cancer 
      cells. In addition, they could be encapsulated with superparamagnetic iron oxide 
      (SPIO) nanoparticles and visualized by MRI in vivo. Preliminary in vivo results 
      demonstrated the low toxicity of these particles and their use in 
      chemo-radiotherapy to effectively reduce lung tumors. These results indicate that 
      MDNPs can potentially be used as nano-vehicles to provide simultaneous 
      chemotherapy and radiation sensitization for lung cancer treatment.
FAU - Menon, Jyothi U
AU  - Menon JU
AD  - Bioengineering Department, University of Texas at Arlington, Arlington, TX, 
      76019, USA.
AD  - Graduate Biomedical Engineering Program at UT Southwestern Medical Center at 
      Dallas, Dallas, TX, 75390, USA.
FAU - Kuriakose, Aneetta
AU  - Kuriakose A
AD  - Bioengineering Department, University of Texas at Arlington, Arlington, TX, 
      76019, USA.
AD  - Graduate Biomedical Engineering Program at UT Southwestern Medical Center at 
      Dallas, Dallas, TX, 75390, USA.
FAU - Iyer, Roshni
AU  - Iyer R
AD  - Bioengineering Department, University of Texas at Arlington, Arlington, TX, 
      76019, USA.
AD  - Graduate Biomedical Engineering Program at UT Southwestern Medical Center at 
      Dallas, Dallas, TX, 75390, USA.
FAU - Hernandez, Elizabeth
AU  - Hernandez E
AD  - Department of Urology at UT Southwestern Medical Center, Dallas, TX, 75390, USA.
FAU - Gandee, Leah
AU  - Gandee L
AD  - Department of Urology at UT Southwestern Medical Center, Dallas, TX, 75390, USA.
FAU - Zhang, Shanrong
AU  - Zhang S
AD  - Advanced Imaging Research Center at UT Southwestern Medical Center, Dallas, TX, 
      75390, USA.
FAU - Takahashi, Masaya
AU  - Takahashi M
AD  - Advanced Imaging Research Center at UT Southwestern Medical Center, Dallas, TX, 
      75390, USA.
FAU - Zhang, Zhang
AU  - Zhang Z
AD  - Department of Radiation Oncology at UT Southwestern Medical Center, Dallas, TX, 
      75390, USA.
AD  - Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, 
      TX, 75390, USA.
FAU - Saha, Debabrata
AU  - Saha D
AD  - Department of Radiation Oncology at UT Southwestern Medical Center, Dallas, TX, 
      75390, USA. debabrata.saha@utsouthwestern.edu.
AD  - Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, Dallas, 
      TX, 75390, USA. debabrata.saha@utsouthwestern.edu.
FAU - Nguyen, Kytai T
AU  - Nguyen KT
AD  - Bioengineering Department, University of Texas at Arlington, Arlington, TX, 
      76019, USA. knguyen@uta.edu.
AD  - Graduate Biomedical Engineering Program at UT Southwestern Medical Center at 
      Dallas, Dallas, TX, 75390, USA. knguyen@uta.edu.
LA  - eng
GR  - R01 HL118498/HL/NHLBI NIH HHS/United States
GR  - R21 CA175879/CA/NCI NIH HHS/United States
GR  - U01 HL111146/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20171016
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antineoplastic Agents)
RN  - 0 (carboxymethyl-chitosan)
RN  - 9012-76-4 (Chitosan)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage/chemistry/*therapeutic use
MH  - Cell Line, Tumor
MH  - Chitosan/analogs & derivatives/chemistry
MH  - Drug Delivery Systems/*methods
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Nanoparticles/*chemistry
PMC - PMC5643549
COIS- The authors declare that they have no competing interests.
EDAT- 2017/10/19 06:00
MHDA- 2019/06/30 06:00
PMCR- 2017/10/16
CRDT- 2017/10/18 06:00
PHST- 2017/07/03 00:00 [received]
PHST- 2017/09/20 00:00 [accepted]
PHST- 2017/10/18 06:00 [entrez]
PHST- 2017/10/19 06:00 [pubmed]
PHST- 2019/06/30 06:00 [medline]
PHST- 2017/10/16 00:00 [pmc-release]
AID - 10.1038/s41598-017-13320-4 [pii]
AID - 13320 [pii]
AID - 10.1038/s41598-017-13320-4 [doi]
PST - epublish
SO  - Sci Rep. 2017 Oct 16;7(1):13249. doi: 10.1038/s41598-017-13320-4.